Hypersensitivity pneumonitis (HP) is one of those Step 1 “pattern recognition” diseases: a restrictive/interstitial lung disease caused by repeated inhalation of an antigen, leading to immune-mediated inflammation of the alveoli and small airways. The test loves it because it blends immunology (Type III/IV hypersensitivity) with pulmonology (restrictive PFTs + decreased DLCO) and a classic occupational/environmental exposure story.
Where it fits (big picture)
HP is an interstitial lung disease (ILD) that primarily affects:
- Alveoli
- Terminal bronchioles
- Interstitial tissue
It can present as acute, subacute, or chronic disease—often depending on intensity and duration of exposure.
Step clue: Restrictive symptoms + exposure history + imaging showing ground-glass or centrilobular nodules (early) or fibrosis (late) = think HP.
Definition (what it is)
Hypersensitivity pneumonitis is an immune-mediated lung disease caused by inhaled organic antigens (or certain chemicals) that trigger:
- Immune complex–mediated inflammation (Type III) and
- T-cell–mediated delayed hypersensitivity (Type IV)
This leads to alveolitis, small airway inflammation, and in chronic cases, fibrosis.
First Aid cross-reference: Commonly appears under Interstitial lung diseases and Hypersensitivity pneumonitis (often alongside pneumoconioses, sarcoidosis, idiopathic pulmonary fibrosis).
High-yield exposures (know these cold)
Classic antigen sources
| Nickname / Setting | Common Antigen Source | High-yield clue |
|---|---|---|
| Farmer’s lung | Moldy hay (thermophilic actinomycetes) | Fevers/cough after handling hay |
| Bird fancier’s lung | Bird droppings/feathers (avian proteins) | Pigeon/parakeet exposure |
| Hot tub lung | Mycobacterium avium complex aerosol | Symptoms after hot tub use (immune reaction, not classic infection) |
| Malt worker’s lung | Mold spores from barley | Brewery/malt facility exposure |
| Humidifier/AC lung | Contaminated water reservoirs | Office/home HVAC exposure |
Exam pitfall: HP is from inhaled antigens; eosinophilia/asthma-like atopy points more toward allergic asthma or ABPA, not classic HP.
Pathophysiology (why it happens)
Immunology core
Repeated exposure causes:
- Type III hypersensitivity
- Antigen + IgG → immune complexes
- Complement activation → neutrophilic inflammation
- Type IV hypersensitivity
- Th1-mediated delayed reaction
- Granulomatous inflammation
Tissue-level consequences
- Interstitial inflammation (alveolitis)
- Bronchiolitis (small airways)
- Noncaseating granulomas (often described as “poorly formed”)
- With chronic exposure → fibrosis, architectural distortion, and restrictive physiology
Buzzwords
- “Noncaseating granulomas” (but think: not the same clinical package as sarcoidosis)
- “Lymphocytic alveolitis”
- “Poorly formed granulomas” (a common pathology phrasing for HP)
Clinical presentation (what you see)
Acute HP (hours after exposure)
- Fever, chills
- Dry cough
- Dyspnea
- Chest tightness, malaise
- Symptoms often occur 4–8 hours after exposure and improve with antigen avoidance
Subacute / Chronic HP (weeks to years)
- Progressive exertional dyspnea
- Chronic cough
- Fatigue, weight loss
- End-inspiratory crackles
- In chronic disease: possible clubbing (from fibrosis)
Step-style stem: A bird owner with episodic fevers + cough after cleaning the cage; later develops progressive dyspnea and restrictive lung disease.
Diagnosis (how to lock it in)
HP is a clinic + exposure + imaging diagnosis supported by labs/bronchoscopy, and occasionally biopsy.
1) Pulmonary function tests (PFTs)
- Restrictive pattern
- ↓ TLC
- ↓ FVC (often with normal/↑ FEV1/FVC ratio)
- ↓ DLCO (gas exchange impairment due to interstitial involvement)
2) Imaging
Chest X-ray
- Can be normal early
- Diffuse interstitial pattern in more established disease
High-resolution CT (HRCT)
- Ground-glass opacities (active inflammation)
- Centrilobular nodules
- Mosaic attenuation / air trapping (small airway involvement)
- Chronic: fibrotic changes (reticulation, traction bronchiectasis)
High-yield contrast
- HP often has airway-centered findings (air trapping/mosaic attenuation) because bronchioles are involved.
3) Bronchoalveolar lavage (BAL)
- Lymphocytosis is classic (often CD8-predominant in many teaching schemas)
- Helps distinguish from diseases with more neutrophils/eosinophils depending on context
4) Serology (supportive, not definitive)
- Precipitating IgG antibodies to the offending antigen can be present
- Helpful for exposure confirmation
- Not perfectly specific (exposure ≠ disease)
5) Histology (if needed)
- Interstitial lymphocytic infiltrates
- Poorly formed noncaseating granulomas
- Bronchiolocentric distribution
Treatment (what to do)
Cornerstone: antigen avoidance
- Remove the exposure (birds, moldy hay, contaminated humidifier, etc.)
- Workplace/environment modifications (ventilation, PPE, remediation)
Pharmacologic therapy
- Systemic corticosteroids can help in acute/subacute disease or significant symptoms:
- Reduce inflammation more quickly
- Do not replace avoidance
- Chronic fibrotic HP may respond less dramatically; goal becomes:
- Prevent progression
- Manage hypoxemia and complications
Supportive care (esp. chronic disease)
- Oxygen if hypoxemic
- Pulmonary rehab
- Vaccinations (flu, pneumococcal)
- In advanced end-stage fibrosis: consider transplant evaluation
How to distinguish HP from similar Step diseases
HP vs Asthma
| Feature | Hypersensitivity pneumonitis | Asthma |
|---|---|---|
| Primary site | Alveoli + interstitium + small airways | Bronchi |
| Hypersensitivity type | Type III + Type IV | Mostly Type I (IgE) |
| PFTs | Restrictive, ↓ DLCO | Obstructive, DLCO usually normal/↑ |
| Key clue | Antigen exposure + systemic symptoms (fever) | Atopy, wheeze, triggers |
HP vs Sarcoidosis
| Feature | HP | Sarcoidosis |
|---|---|---|
| Trigger | Inhaled antigen exposure | Idiopathic; systemic granulomatous disease |
| Granulomas | Poorly formed noncaseating | Well-formed noncaseating |
| Imaging clue | Ground-glass, centrilobular nodules, air trapping | Bilateral hilar adenopathy (classic) |
| Systemic findings | Less stereotyped; exposure-driven | Can have erythema nodosum, uveitis, hypercalcemia |
HP vs Idiopathic Pulmonary Fibrosis (IPF)
| Feature | HP | IPF |
|---|---|---|
| Cause | Known antigen exposure | Idiopathic |
| Onset | Acute/subacute episodes possible | Insidious, progressive |
| HRCT | Ground-glass/nodules/air trapping; may fibrose | Subpleural honeycombing, basilar predominance |
| Treatment focus | Avoid antigen ± steroids | Antifibrotics (Step-level: know it’s progressive) |
High-yield associations & “testable one-liners”
- HP is an immune-mediated ILD due to repeated inhalation of antigens.
- Mechanism: Type III (immune complex) + Type IV (T-cell–mediated) hypersensitivity.
- PFTs: restrictive + ↓ DLCO.
- HRCT: ground-glass, centrilobular nodules, mosaic attenuation/air trapping.
- BAL: lymphocytosis.
- Path: poorly formed noncaseating granulomas + interstitial inflammation.
- Treatment: antigen avoidance is #1; corticosteroids can help reduce inflammation, especially early.
Rapid Step 1/2 checkpoint (mini drill)
If the stem says:
- “Bird owner” + episodic fevers/dyspnea a few hours after cleaning cages → HP
- “Moldy hay” + cough/dyspnea → HP
- PFTs show restrictive + ↓ DLCO and CT shows ground-glass + air trapping → HP
- Granulomas but no hilar adenopathy story and a clear exposure → HP > sarcoid